Niemann- Pick Disease

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Niemann-Pick Disease is one of a group of lysosomal storage diseases that affect metabolism and that are caused by genetic mutations. The three most commonly recognized forms are Niemann-Pick Types A and B (ASMD or Acid Sphingomyelinase Deficiency) and Niemann-Pick Disease Type C (NPC).Niemann–Pick diseases are a subgroup of lipid storage disorders called sphingolipidoses in which harmful quantities of fatty substances, or lipids, accumulate in the spleen, liver, lungs, bone marrow, and brain. In the classic infantile type-A variant, a missense mutation causes complete deficiency of sphingomyelinase. Sphingomyelin is a component of cell membrane including the organellar membrane, so the enzyme deficiency blocks degradation of lipid, resulting in the accumulation of sphingomyelin within lysosomes in the macrophage-monocyte phagocyte lineage. Affected cells become enlarged, sometimes up to 90 μm in diameter, secondary to the distention of lysosomes with sphingomyelin and cholesterol. Histology shows lipid-laden macrophages in the marrow and "sea-blue histiocytes" on pathology. Numerous small vacuoles of relatively uniform size are created, giving the cytoplasm a foamy appearance.

Several treatment options, including bone marrow transplants, enzyme replacement therapy, and gene therapy have been used. Research is ongoing to determine the effectiveness of such treatments. A medication called miglustat is currently used to treat type C. Miglustat is classified as an enzyme inhibitor, and works by preventing the body from producing fatty substances (in the case of type C, cholesterol) so that less of it will build up in the body. And there is no treatment for type A and D.Bone marrow transplants have been done on a few patients with type B with encouraging results. Researchers continue to study possible treatments, including enzyme replacement and gene therapy. Results of a survey shows the extrapolation of Prevalence Rate of Niemann-Pick disease type C2 in Finland is 34 for the estimated total population of 5,21,45,122There is current research aiming to develop recombinant human acid sphingomyelinase for the potential treatment of NP disease types A and B. A phase 1 clinical trial was completed in 2009. A phase 2 trial is planned.